STEAP: A prostate-specific cell-surface antigen highly expressed in human prostate tumors
STEAP: A prostate-specific cell-surface antigen highly expressed in human prostate tumors
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DOI：
10.1073/pnas.96.25.14523
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发表时间：
1999-12-07
影响因子：
11.1
通讯作者：
Afar, DEH
中科院分区：
文献类型：
--
作者：
Hubert, RS;Vivanco, I;Afar, DEH
为了寻找在转移性前列腺癌中表达的新基因，我们从模拟晚期疾病的前列腺癌异种移植模型中分离的cDNA中减去从良性前列腺肥大组织中分离的cDNA。一个在晚期前列腺癌中高度表达的新基因编码一个339个氨基酸的蛋白质，该蛋白质具有六个潜在的跨膜区域，两侧是亲水性氨基和羧基末端结构域。这种结构暗示了作为通道或转运蛋白的潜在功能。该基因被命名为STEAP（前列腺六跨膜上皮抗原），主要在人类前列腺组织中表达，并在多种癌细胞系中表达上调，包括前列腺、膀胱、结肠癌、卵巢癌和尤文氏肉瘤。临床标本免疫组化分析显示STEAP在前列腺和前列腺癌细胞分泌上皮的细胞-细胞连接处有显著表达。在正常的非前列腺组织的质膜上几乎没有染色，除了膀胱组织，在细胞膜上表达低水平的STEAP。蛋白质分析发现STEAP位于前列腺癌细胞的细胞表面。我们的研究结果支持STEAP作为前列腺癌治疗和诊断成像的细胞表面肿瘤抗原靶点。
In search of novel genes expressed in metastatic prostate cancer, we subtracted cDNA isolated from benign prostatic hypertrophic tissue from cDNA isolated from a prostate cancer xenograft model that mimics advanced disease. One novel gene that is highly expressed in advanced prostate cancer encodes a 339-amino acid protein with six potential membrane-spanning regions flanked by hydrophilic amino- and carboxyl-terminal domains. This structure suggests a potential function as a channel or transporter protein. This gene, named STEAP for six-transmembrane epithelial antigen of the prostate, is expressed predominantly in human prostate tissue and is up-regulated in multiple cancer cell lines, including prostate, bladder, colon, ovarian, and Ewing sarcoma. Immunohistochemical analysis of clinical specimens demonstrates significant STEAP expression at the cell-cell junctions of the secretory epithelium of prostate and prostate cancer cells. Little to no staining was detected at the plasma membranes of normal, nonprostate human tissues, except for bladder tissue, which expressed low levels of STEAP at the cell membrane. Protein analysis located STEAP at the cell surface of prostate-cancer cell lines. Our results support STEAP as a cell-surface tumor-antigen target for prostate cancer therapy and diagnostic imaging.